Abstracts of the Fourth Brainstorming Research Assembly for Young Neuroscientists (BraYn), Italy, 20–22 October 2021

On behalf of the BraYn Association, we are pleased to present the Abstracts of the Fourth Brainstorming Research Assembly for Young Neuroscientists, which was held from 20–22 October 2021. We congratulate all the presenters on their research work and contribution.

Ibrutinib in Refractory or Relapsing Primary Central Nervous System Lymphoma: A Systematic Review

Primary Central Nervous System Lymphoma (PCNSL) is a rare variant of Non-Hodgkin Lymphoma (NHL) representing 1–2% of all NHL cases. PCNSL is defined as a lymphoma that occurs in the brain, spinal cord, leptomeninges, or eyes. Efforts to treat PCNSL by traditional chemotherapy and radiotherapy have generally been unsuccessful as a significant proportion of patients have frequent relapses or are refractory to treatment. The prognosis of patients with Refractory or Relapsed (R/R) PCNSL is abysmal. The optimal treatment for R/R PCNSL is poorly defined as there are only a limited number of studies in this setting. Several studies have recently shown that ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor, has promising results in the treatment of R/R PCNSL. However, these are preliminary studies with a limited sample size. In this systematic review, we explored and critically appraised the evidence about the efficacy of the novel agent ibrutinib in treating R/R PCNSL.

Financial Incapacity of Patients with Mild Alzheimer’s Disease: What Neurologists Need to Know about Where the Impairment Lies

Research in the last decade has focused on assessing financial capacity and incapacity mainly in old age, but new research has turned to address the question of how financial incapacity can be predicted by cognitive factors. The aim of this study was to identify which cognitive domains predict financial capacity and the relevant cognitive skills of patients with mild Alzheimer’s disease (AD) in order to assist neurologists in functional assessment and further patient referral. In this study, 109 patients diagnosed with mild AD were examined with a number of neuropsychological tests: Mini-Mental State Examination (MMSE), Functional Rating Scale for Symptoms of Dementia (FRSSD), Functional Cognitive Assessment Scale (FUCAS), Trail Making Test (TMT)-Part B, Rey-Osterrieth Complex Figure Test (ROCFT)-copy condition and delayed recall condition, Rey Auditory Verbal Learning Test (RAVLT), Boston Naming Test, Rivermead Behavioural Memory Test (RBMT), digit span forward and backward, WAIS-R digit symbol substitution test, Neuropsychiatric Inventory (NPI), Geriatric Depression Scale (GDS-15), and the Legal Capacity for Property Law Transactions Assessment Scale (LCPLTAS). LCPLTAS total score and relevant subdomains were best predicted only by the score of one item coming from MMSE: subtraction of serial sevens. This is the only measure of arithmetic testing in use for the Greek geriatric population. Financial capacity is severely impaired in the group of mild AD patients. In order to prevent financial exploitation cases, neurologists, neuropsychologists, psychiatrists, and geriatrists should pay close attention to the information from the relevant arithmetic question of MMSE, as it is one of the most widely administered screening tests in clinical settings.

COVID-19 Is Changing Our Understanding of the Neuroscience of Viral Infections: What We Can Do to Prepare for the Future?

In the approximately two years since the emergence of COVID-19 (Coronavirus Disease 2019) myriad neurological symptoms have been reported that are seemingly unrelated to each other [...]

Bremelanotide for Treatment of Female Hypoactive Sexual Desire

Hypoactive sexual desire disorder (HSDD) is a persistent deficiency or absence of sexual fantasies and desire resulting in significant distress or interpersonal difficulty. Women with this disorder may display a lack of motivation for sexual activity, reduced responsiveness to erotic cues, a loss of interest during sexual activity, and avoidance of situations that could lead to sexual activity. The pathophysiology of HSDD is thought to be centered around inhibitory and excitatory hormones, neurotransmitters, and specific brain anatomy. Due to the multifactorial nature of HSDD, treatment can be complex and must attempt to target the biological and psychosocial aspects of the disorder. Bremelanotide is a melanocortin receptor agonist and has been recently approved by the FDA to treat HSDD. Bremelanotide is administered intranasally or as a subcutaneous injection. The recommended dosage of bremelanotide is 1.75 mg injected subcutaneously in the abdomen or thigh at least 45 min before sexual activity. Studies showed improvements in desire, arousal, and orgasm scores when 1.75 mg of bremelanotide was administered before sexual activity compared to a placebo. Bremelanotide is a promising way to treat HSDD.

Antipsychotic Use in Pregnancy: Patient Mental Health Challenges, Teratogenicity, Pregnancy Complications, and Postnatal Risks

Pregnant women constitute a vulnerable population, with 25.3% of pregnant women classified as suffering from a psychiatric disorder. Since childbearing age typically aligns with the onset of mental health disorders, it is of utmost importance to consider the effects that antipsychotic drugs have on pregnant women and their developing fetus. However, the induction of pharmacological treatment during pregnancy may pose significant risks to the developing fetus. Antipsychotics are typically introduced when the nonpharmacologic approaches fail to produce desired effects or when the risks outweigh the benefits from continuing without treatment or the risks from exposing the fetus to medication. Early studies of pregnant women with schizophrenia showed an increase in perinatal malformations and deaths among their newborns. Similar to schizophrenia, women with bipolar disorder have an increased risk of relapse in antepartum and postpartum periods. It is known that antipsychotic medications can readily cross the placenta, and exposure to antipsychotic medication during pregnancy is associated with potential teratogenicity. Potential risks associated with antipsychotic use in pregnant women include congenital abnormalities, preterm birth, and metabolic disturbance, which could potentially lead to abnormal fetal growth. The complex decision-making process for treating psychosis in pregnant women must evaluate the risks and benefits of antipsychotic drugs.

Naltrexone Implant for Opioid Use Disorder

The continued rise in the availability of illicit opioids and opioid-related deaths in the United States has left physicians, researchers, and lawmakers desperate for solutions to this ongoing epidemic. The research into therapeutic options for the treatment of opioid use disorder (OUD) began with the introduction of methadone in the 1960s. The approval of oral naltrexone initially showed much promise, as the drug was observed to be highly potent in antagonizing the effects of opioids while producing no opioid agonist effects of its own and having a favorable side effect profile. Patients that routinely take their naltrexone reported fewer days of heroin use and had more negative drug tests than those without treatment. Poor outcomes in OUD patients treated with naltrexone have been directly tied to short treatment time. Studies have shown that naltrexone given orally vs. as an implant at the 6-month interval showed a higher non-compliance rate among those who used oral medications at the 6-month mark and a slower return to use rate. There were concerns that naltrexone could possibly worsen negative symptoms seen in opiate use disorder related to blockade of endogenous opioids that are important for pleasurable stimuli. Studies have shown that naltrexone demonstrated no increase in levels of anxiety, depression and anhedonia in participants and another study found that those treated with naltrexone had a significant reduction in mental health-related hospitalizations. The latter study also concluded that there was no increased risk for mental health-related incidents in patients taking naltrexone via a long-acting implant. Although not yet FDA approved in the United States, naltrexone implant has shown promising results in Europe and Australia and may provide a novel treatment option for opioid addiction.

Guillain-Barré Syndrome in the COVID-19 Pandemic

There have been several reported cases of severe acute respiratory syndrome (SARS-CoV-2) infection that were associated with an increased incidence of neurological manifestations, including Guillain–Barré syndrome (GBS). This review aims to present information on the reports of GBS associated with coronavirus disease 2019 (COVID-19) infection. Our review is retrospective work examining articles published from the 1 April 2020 to the 8 May 2021 in the English language. We used the diagnostic criteria and classification published by the National Institute of Neurological Disorders and Stroke and Brighton Collaboration. GBS is usually a postinfectious syndrome, but GBS in the COVID-19 pandemic also takes on a para-infectious profile. In the reports, the genetic factor has a role in developing GBS in some patients. In conclusion, the association between COVID-19 and GBS is not very clear. Still, one mechanism is strongly associated with COVID-19 and immune-mediated neurological complications, which is molecular mimicry between SARS-CoV-2 and human autoantigens.

Hypomyelinating Leukodystrophy 7 (HLD7)-Associated Mutation of POLR3A Is Related to Defective Oligodendroglial Cell Differentiation, Which Is Ameliorated by Ibuprofen

Hypomyelinating leukodystrophy 7 (HLD7) is an autosomal recessive oligodendroglial cell-related myelin disease, which is associated with some nucleotide mutations of the RNA polymerase 3 subunit a (polr3a) gene. POLR3A is composed of the catalytic core of RNA polymerase III synthesizing non-coding RNAs, such as rRNA and tRNA. Here, we show that an HLD7-associated nonsense mutation of Arg140-to-Ter (R140X) primarily localizes POLR3A proteins as protein aggregates into lysosomes in mouse oligodendroglial FBD−102b cells, whereas the wild type proteins are not localized in lysosomes. Expression of the R140X mutant proteins, but not the wild type proteins, in cells decreased signaling through the mechanistic target of rapamycin (mTOR), controlling signal transduction around lysosomes. While cells harboring the wild type constructs exhibited phenotypes with widespread membranes with myelin marker protein expression following the induction of differentiation, cells harboring the R140X mutant constructs did not exhibit them. Ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), which is also known as an mTOR signaling activator, ameliorated defects in differentiation with myelin marker protein expression and the related signaling in cells harboring the R140X mutant constructs. Collectively, HLD7-associated POLR3A mutant proteins are localized in lysosomes where they decrease mTOR signaling, inhibiting cell morphological differentiation. Importantly, ibuprofen reverses undifferentiated phenotypes. These findings may reveal some of the pathological mechanisms underlying HLD7 and their amelioration at the molecular and cellular levels.

Co-Designing a New Yoga-Based Mindfulness Intervention for Survivors of Stroke: A Formative Evaluation

Movement-based mindfulness interventions (MBI) are complex, multi-component interventions for which the design process is rarely reported. For people with stroke, emerging evidence suggests benefits, but mainstream programs are generally unsuitable. We aimed to describe the processes involved and to conduct a formative evaluation of the development of a novel yoga-based MBI designed for survivors of stroke. We used the Medical Research Council complex interventions framework and principles of co-design. We purposefully approached health professionals and consumers to establish an advisory committee for developing the intervention. Members collaborated and iteratively reviewed the design and content of the program, formatted into a training manual. Four external yoga teachers independently reviewed the program. Formative evaluation included review of multiple data sources and documentation (e.g., formal meeting minutes, focus group discussions, researcher observations). The data were synthesized using inductive thematic analysis. Three broad themes emerged: (a) MBI content and terminology; (b) manual design and readability; and (c) barriers and enablers to deliver the intervention. Various perspectives and feedback on essential components guided finalizing the program. The design phase of a novel yoga-based MBI was strengthened by interdisciplinary, consumer contributions and peer review. The 12-week intervention is ready for testing among survivors of stroke.